crossing96/oncoscreening huggingface dataset:
PFKFB4 as a prognostic marker in non-muscle-invasive bladder cancer.	OBJECTIVES: PFKFB4 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4) is induced by hypoxia and is strongly associated with glycolysis. Previously, we reported that PFKFB4 expression level may serve as a predictor of progression in non-muscle-invasive bladder cancer (NMIBC). Here, the role of PFKFB4 in NMIBC and the relationship between PFKFB4 expression and biological behavior in bladder cancer was investigated. METHODS: One hundred ninety-three primary NMIBC tissue specimens were analyzed by real-time PCR. Immunohistochemical staining was performed on 77 subsets of tumor samples. The results were compared with clinicopathologic parameters, and the Kaplan-Meier method and a multivariate Cox regression model were used to identify the prognostic value of PFKFB4 for recurrence and progression. RESULTS: The mRNA expression levels of PFKFB4 were significantly higher in patients with high stage carcinoma and multiple tumors as compared to low stage and single tumors (P < 0.05 for each). Kaplan-Meier estimates revealed significant differences in time to recurrence and progression between low- and high-mRNA expression groups (log-rank test, P = 0.015 and 0.003, respectively). Multivariate Cox regression analysis revealed that the level of PFKFB4 expression is an independent predictor of bladder tumor progression (HR, 2.026; 95% CI, 1.177-3.488; P = 0.011). Immunohistochemical findings were generally concordant with mRNA expression levels. CONCLUSIONS: PFKFB4 has an important role in the progression of NMIBC, and may serve as a useful prognostic indicator for bladder cancer progression.	bladder
Water disinfection by-products and bladder cancer: is there a European specificity? A pooled and meta-analysis of European case-control studies.	Several epidemiological studies suggested an association between the risk of bladder cancer and the exposure to trihalomethanes (THMs), the main disinfection by-products (DBPs) of chlorinated water. A previous pooled analysis of case-control studies from North America and Europe estimated a summarized dose-response relation. For policy guidance of drinking water disinfection in Europe and because major differences exist in water disinfection practices and DBPs occurrence between both continents, specific risk estimates for bladder cancer in relation to DBPs exposure for European populations were needed. We conducted a pooled and a two-stage random-effect meta-analyses of three European case-control studies from France, Finland, and Spain (5467 individuals: 2381 cases and 3086 controls). Individual exposure to THMs was calculated combining information on residential history, estimates of the average total THMs (TTHM) level in tap water at the successive residences and personal water consumption. A significant odds-ratio was observed for men exposed to an average residential TTHM level > 50 μg/l (OR = 1.47 (1.05; 2.05)) when compared to men exposed to levels ≤ 5 μg/l. The linear trend of the exposure-risk association was significant (p = 0.01). Risks increased significantly for exposure levels above 25 μg/l and with more than 30 years of exposure to chlorinated water, but were mainly driven by the level rather than the duration of exposure. No significant association was found among women or with cumulative exposure through ingestion. There was no evidence of a differential exposure-response relation for TTHM and bladder cancer in Europe and North America. Consequently, a global exposure-risk relation based on 4351 cases and 7055 controls is now available.	bladder
Loss of p53 and acquisition of angiogenic microRNA profile are insufficient to facilitate progression of bladder urothelial carcinoma in situ to invasive carcinoma.	Activation of oncogenes or inactivation of tumor suppressors in urothelium is considered critical for development of urothelial cancer. Here we report cloning of the urothelium-specific promoter uroplakin-II (UPK II) and generation of transgenic mice in which expression of SV40 large T antigen is driven by UPK II promoter. Inactivation of tumor suppressor p53 and pRb in urothelium by SV40 T antigen resulted in urothelial carcinoma, resembling human high-grade carcinoma in situ. Specific deletion of p53 in urothelial cells using the newly generated UPK II-Cre mice results in normal bladders without any evidence of cancer. The high-grade carcinoma in situ in the UPK II-SV40 mice is associated with significant activation of angiogenic signals consisting of hypoxia-inducible factor-1α (HIF-1α) and VEGF and a down-regulation of thrombospondin-1. Interestingly, such pro-angiogenic activity was not associated with progression to invasive cancer. Analysis of bladder-associated microRNAs in carcinoma in situ lesions reveals a pro-angiogenic profile, with specific overexpression of miR-18a and miR-19a and down-regulation of miR-107. A group of microRNAs (miRs) identified as associated with invasive human urothelial cancer remained unchanged in this mouse model. Collectively, our results support the notion that activation of angiogenesis and loss of p53 are not sufficient for progression to invasive cancer. Our studies identify a new mouse model for bladder cancer that can be used to study factors that determine progression to an invasive phenotype of bladder cancer.	bladder
Lymphoepithelioma-like carcinoma of the urinary bladder: clinicopathologic, immunohistochemical, and molecular features.	INTRODUCTION: Lymphoepithelioma-like carcinoma (LELC) in the urinary tract is a rare malignancy, named for its resemblance to nasopharyngeal undifferentiated carcinoma or lymphoepithelioma. Investigation of immunohistochemical and molecular characteristics of bladder LELC is limited. The pathogenesis and biological behavior of these tumors are controversial. MATERIALS AND METHODS: We examined clinicopathologic features of the urinary tract LELC, including light microscopy; immunohistochemistry for cytokeratin 7 (CK7), CK20, 34βE12, p53, p63, α-methylacyl-CoA racemase, thyroid transcription factor-1, Epstein-Barr virus latent membrane protein-1, and CD30; in situ hybridization for human papillomavirus; and UroVysion fluorescence in situ hybridization (FISH). RESULTS: We identified tumors from 34 patients, the largest series to date, (male:female, 2.8:1), ranging from 54 to 84 years of age (mean, 70 years). Urothelial carcinoma in situ was identified in 50% of patients. 34βE12 (75%), CK7 (57%), and p63 (53%) were frequently positive in tumor cells, whereas thyroid transcription factor-1 and CD30 were consistently negative. Expression of p53 was noted in a subset of tumors (61%), whereas CK20 staining was negative with weak positivity in a single case. UroVysion FISH showed frequent chromosomal abnormalities similar to those of urothelial carcinoma. In tumors with concurrent urothelial, squamous, sarcomatoid, and glandular components, identical FISH abnormalities were noted in both areas. In situ hybridization for human papillomavirus and immunostaining for Epstein-Barr virus were negative in all studied lesions. Five patients with pure or predominant LELC tumors treated with transurethral resection and followed by chemotherapy were alive without evidence of disease at 2 to 5 years. In contrast, 2 patients treated in this manner with <50% LELC morphology had death from disease or distant metastasis. DISCUSSION: Urinary tract LELC is a rare histologic variant of urothelial carcinoma. The frequent presence of UroVysion FISH abnormalities, urothelial carcinoma in situ, and p53 positivity by immunohistochemistry in cases of urinary tract LELC suggests a similar pathogenesis to high-grade invasive urothelial carcinoma. In contrast to typical urothelial carcinoma, CK20 is frequently negative in LELC. Our findings support the hypothesis that pure or predominant LELC may be treated with transurethral resection and chemotherapy. However, a large-scale study with long-term follow-up is needed to better understand the biological behavior of urinary bladder LELC.	bladder
Polypoid endometriosis of the bladder during pregnancy mimicking urachal carcinoma.	We report a case of polypoid bladder endometriosis in pregnancy. Diagnostic workup showed a vesicouterine well-vascularized polypoid mass, suspicious for malignancy. During pregnancy, the mass was surgically resected with safe oncological margins. Pathological examination of the resected specimen revealed pseudotumoral polypoid endometriosis of the bladder. We illustrate diagnostic pitfalls in the differentiation between bladder endometriosis during pregnancy and malignancy. As a result of pregnancy-related decidualization of vesical endometriosis, differentiation between this rare occurrence and malignant transformation is challenging.	bladder
CDCOCA: a statistical method to define complexity dependence of co-occuring chromosomal aberrations.	BACKGROUND: Copy number alterations (CNA) play a key role in cancer development and progression. Since more than one CNA can be detected in most tumors, frequently co-occurring genetic CNA may point to cooperating cancer related genes. Existing methods for co-occurrence evaluation so far have not considered the overall heterogeneity of CNA per tumor, resulting in a preferential detection of frequent changes with limited specificity for each association due to the high genetic instability of many samples. METHOD: We hypothesize that in cancer some linkage-independent CNA may display a non-random co-occurrence, and that these CNA could be of pathogenetic relevance for the respective cancer. We also hypothesize that the statistical relevance of co-occurring CNA may depend on the sample specific CNA complexity. We verify our hypotheses with a simulation based algorithm CDCOCA (complexity dependence of co-occurring chromosomal aberrations). RESULTS: Application of CDCOCA to example data sets identified co-occurring CNA from low complex background which otherwise went unnoticed. Identification of cancer associated genes in these co-occurring changes can provide insights of cooperative genes involved in oncogenesis. CONCLUSIONS: We have developed a method to detect associations of regional copy number abnormalities in cancer data. Along with finding statistically relevant CNA co-occurrences, our algorithm points towards a generally low specificity for co-occurrence of regional imbalances in CNA rich samples, which may have negative impact on pathway modeling approaches relying on frequent CNA events.	bladder
Treatment efficiency, outcome and surgical treatment problems in patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma: a report from the Cooperative Soft Tissue Sarcoma trial CWS-96.	BACKGROUND: To analyze the clinical course, treatment modalities, complications and outcome of patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma (BPRMS) treated on the CWS-96 trial. PROCEDURE: There were 85 patients with BPRMS enrolled and 63 patients with embryonal non-metastatic BPRMS were analyzed. Fifty-six patients received neoadjuvant chemotherapy and response was assessed radiographically after 9 weeks. Local therapy with radiation and or surgery was performed based on age, tumor size, and response. Patients were treated with adjuvant chemotherapy following local control. RESULTS: Patient's age ranged from 0 to 16 years with a median follow up of 5.3 years. Eighty nine percent of the patients had IRS group III disease. The 5-year overall survival (OS) for the whole group was 76.3 ± 5.6% and the 5-year event-free survival (EFS) 69.8 ± 6.2%. Seventeen patients underwent preoperative radiochemotherapy followed by tumor resection (5-year-OS: 87.8 ± 8.1%). Eight patients were treated with solely radiochemotherapy (87.5 ± 11.7%). Twenty-five patients received chemotherapy and tumor resection (OS: 83.6 ± 7.5%). Thirteen patients underwent incomplete tumor resection and were treated with radiochemotherapy postoperatively (OS: 39.9 ± 14.8%, P < 0.05 vs. other groups). CONCLUSIONS: Local therapy is an important factor for prognosis of localized embryonal BPRMS. Inadequate primary or secondary surgery compromises the outcome and should be avoided. Radiotherapy alone, complete surgical tumor resection or combined preoperative radiotherapy with surgical resection lead to similar good local control rates and prognosis.	bladder
Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis.	Case-control studies have shown that regular use of nonsteroidal antiinflammatory drugs (NSAIDs) decreases bladder cancer risk, but few cohort studies have evaluated this association. The authors investigated NSAID use and bladder cancer in 3 large prospective studies (NIH-AARP Diet and Health Study; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and U.S. Radiologic Technologists Study). Frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using self-administered questionnaires. Study-specific hazard ratios and 95% confidence intervals were estimated using Cox regression models and were combined using a fixed-effects meta-analytic model. Data from all studies were aggregated, and aggregated hazard ratios were estimated. The analysis included 508,842 individuals, with 2,489 incident cases of bladder cancer. A reduction in risk was observed for individuals who reported regular use (>2 times/week) of nonaspirin NSAIDs compared with those who reported no use (hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.81, 1.04). The risk reduction was limited to nonsmokers (HR = 0.58, 95% CI: 0.41, 0.83) (P(trend) = 0.008) (P(interaction) = 0.02). No association was observed between regular aspirin use and bladder cancer risk (HR = 1.04, 95% CI: 0.94, 1.15). Results suggest that nonaspirin NSAIDs, but not aspirin, are associated with a reduction in risk of bladder cancer, particularly for nonsmokers.	bladder
[Exfoliative urine cytology in the treatment of bladder cancer].	Urine cytology in addition to cystoscopy and transurethral resection is an integral part in diagnostic and follow-up of transitional carcinomas. The WHO-Classification of 2004 distinguishes between low grade and high grade tumours. Cytological diagnosis had to be adjusted to this new classification.Above all cytology has to detect high grade lesions in a reliable manner. The sensitivity for these lesions ranges between 85-95%. Well differentiated transitional cell carcinomas show marginal nuclear alterations compared to normal urothelial cells. Therefore the cytological low grade diagnosis is needless. Well differentiated papillary tumours can be detected with conventional cystoscopy in nearly 100 percent of all cases. This subtype of urothelial carcinomas is characterized by a very low rate of tumour progression despite a relevant rate of tumour recurrence. A negative cytology result combined with a cystoscopically proven papillary bladder tumour implies low grade disease with low risk of tumour progression.	bladder
Expression of NRG1 and its receptors in human bladder cancer.	BACKGROUND: Therapies targeting ERBB2 have shown success in the clinic. However, response is not determined solely by expression of ERBB2. Levels of ERBB3, its preferred heterodimerisation partner and ERBB ligands may also have a role. METHODS: We measured NRG1 expression by real-time quantitative RT-PCR and ERBB receptors by western blotting and immunohistochemistry in bladder tumours and cell lines. RESULTS: NRG1α and NRG1β showed significant coordinate expression. NRG1β was upregulated in 78% of cell lines. In tumours, there was a greater range of expression with a trend towards increased NRG1α with higher stage and grade. Increased expression of ERBB proteins was detected in 15% (EGFR), 20% (ERBB2), 41% (ERBB3) and 0% (ERBB4) of cell lines. High EGFR expression was detected in 28% of tumours, associated with grade and stage (P=0.05; P=0.04). Moderate or high expression of ERBB2 was detected in 22% and was associated with stage (P=0.025). Cytoplasmic ERBB3 was associated with high tumour grade (P=0.01) and with ERBB2 positivity. In cell lines, NRG1β expression was significantly inversely related to ERBB3, but this was not confirmed in tumours. CONCLUSION: There is a wide spectrum of NRG1 and ERBB receptor expression in bladder cancer. In advanced tumours, EGFR, ERBB2 and ERBB3 upregulation is common and there is a relationship between expression of ERBB2 and ERBB3 but not the NRG1 ligand.	bladder
Spatio-temporal patterns of bladder cancer incidence in Utah (1973-2004) and their association with the presence of toxic release inventory sites.	BACKGROUND: The authors analyse the spatio-temporal variations of the incidence of bladder cancer between 1973 and 2004 in Utah at the census tract level (496 areas) to highlight areas of high and low relative risks that remained so throughout the 32 year period. Using these identified areas, a novel strategy is used to carry out a geographical case-control study of association between the risk of bladder cancer and presence of Toxic Release Inventory sites, where areas with stable high RRs are 'case areas' and all remaining areas with stable non increased risks are 'control areas'. RESULTS: The time trend of bladder cancer risk fluctuated over the study period: A steady decrease was observed, followed by an abrupt increase from 1992 to 2004. Using a Bayesian space-time model, 93 census tracts were classified as having an excess relative risk and 81 a lower relative risk, sustained over the 32 years. We showed that these high relative risk areas for bladder cancer were associated with the presence of Toxic Release Inventory sites, after adjusting for the proportion of Latter-Day Saint Church members as an area level proxy for smoking habits. CONCLUSIONS: Our study has demonstrated that the modeling of data in time and space has additional benefits over a purely spatial analysis. In addition to highlighting the areas with high and low relative risks, this model also allows the simultaneous study of persistency of spatial patterns over time and detection of 'unusual' time trends that may warrant further investigation.	bladder
Paclitaxel and cisplatin chemotherapy for metastatic urothelial carcinoma after failure of two courses of platinum-based regimens.	OBJECTIVES: We investigated the outcomes of paclitaxel and cisplatin chemotherapy as an optional regimen for patients with metastatic urothelial carcinoma after failure of two consecutive platinum-based regimens. METHODS: We retrospectively analyzed the data of 21 patients who had evidence of disease progression after two consecutive platinum-based regimens, gemcitabine and cisplatin (GC course), and methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC course) as first-line and second-line treatments. As third-line chemotherapy, patients received paclitaxel (175 mg/m(2)) and cisplatin (70 mg/m(2)) every 3 weeks until disease progression. RESULTS: Complete remission occurred in one patient (4.8%), partial remission occurred in three patients (14.3%) and stable disease occurred in five patients (23.8%). The overall response rate was 19.0% and the overall disease control rate, including stable disease, was 42.9%. The median progression-free survival (PFS) was 3 months (95% CI 3.0-5.0). The median overall survival was 9 months (95% CI 7.0-15.0). Grade 3 to 4 neutropenia appeared in 85.7% of patients. No life-threatening complications were observed. CONCLUSIONS: Paclitaxel and cisplatin chemotherapy could be an optional regimen for patients with metastatic urothelial carcinoma after the failure of two consecutive standard platinum-based regimens.	bladder
In vitro and in vivo evaluation of intravesical docetaxel loaded hydrophobically derivatized hyperbranched polyglycerols in an orthotopic model of bladder cancer.	The objective of this study was to evaluate the tolerability, to establish a dosing regimen, and to evaluate the efficacy of intravesical docetaxel (DTX) formulations in a mouse model of bladder cancer. DTX in commercial formulation (Taxotere, DTX in Tween 80) or loaded in hyperbranched polyglycerols (HPGs) was evaluated. The synthesis and characterization of HPGs with hydrophobic cores and derivatized with methoxy poly(ethylene glycol) in the shell and further functionalized with amine groups (HPG-C(8/10)-MePEG and HPG-C(8/10)-MePEG-NH(2)) is described. Intravesical DTX in either commercial or HPGs formulations (up to 1.0 mg/mL) was instilled in mice with orthotopic bladder cancer xenografts and was well tolerated with no apparent signs of local or systemic toxicities. Furthermore, a single dose of intravesical DTX (0.5 mg/mL) loaded in HPGs was significantly more effective in reducing the tumor growth in an orthotopic model of bladder cancer than the commercial formulation of Taxotere. In addition, DTX-loaded HPG-C(8/10)-MePEG-NH(2) was found to be more effective at lower instillation dose than DTX (0.2 mg/mL)-loaded HPG-C(8/10)-MePEG. Overall, our data show promising antitumor efficacy and safety in a recently validated orthotopic model of bladder cancer. Further research is warranted to evaluate its safety and efficacy in early phase clinical trials in patients refractory to standard intravesical therapy.	bladder
[Value of fluorescence in situ hybridization of urine exfoliative cells in diagnosis of urinary bladder neoplasms].	OBJECTIVE: To investigate the value of fluorescence in situ hybridization (FISH) examination of urine exfoliative cells in the diagnosis of urinary bladder neoplasms. METHODS: The urine samples were collected from 100 patients with suspected urinary bladder neoplasms and 20 normal control subjects. Both FISH examination and cytology study of urine exfoliative cells were conducted with each sample. The specificity and sensitivity of FISH and cytology were analyzed on the basis of bladder biopsy histology. RESULTS: The sensitivity of FISH examination of bladder malignant tumor was 93.5% (87/93), which was much higher than that of cytology (49.5%, 46/93). Biopsies confirmed 88 cases of urothelial carcinoma among the 100 suspected patients, with 46 high grade tumors and 42 low grade tumors; 30 cases of high stage (T(2-4)) and 58 cases of low stage (T(a-1)). The sensitivity of FISH examination of urothelial carcinoma was 94.3%, which was much higher than that of cytology (52.3%). FISH examination was significantly more sensitive than cytology for low grade and low stage urothelial carcinoma, as well as for rare non-urothelial malignancies (P < 0.05). The specificity of FISH and cytology of bladder malignancies was 92.6% (25/27) and 96.3% (26/27), for urothelial carcinoma was 81.3% (26/32) and 96.9% (31/32), respectively. CONCLUSION: FISH shows high sensitivity and relatively high specificity for the detection of urinary bladder neoplasms, especially for the diagnosis of low grade urothelial carcinoma and non-urothelial malignancies, which were difficult to be detected by cytology.	bladder
[Bladder urothelial carcinoma with acrometastasis: a case report and review of the literature].	The authors report a new case of acrometastasis of the hand, from a urothelial carcinoma of the bladder, in a 46-year-old woman, with a history of left lower lobectomy for bronchial carcinoma. Physical examination revealed a tumor of the dorsal hand, inflammatory and painful. The radiograph showed ill-defined osteolysis of the base of the fourth metacarpal. Two immunohistochemical studies were needed to confirm the origin of the bladder metastasis. The authors propose a review of the literature addressing the difficulty of diagnosis, treatment and poor prognosis of these lesions.	bladder